Polycystic ovary syndrome (PCOS) is considered one of the leading endocrine disorders affecting up to 10% of all women of reproductive age.1 It is a complex disorder stemming from inappropriate hypothalamic-pituitary- ovarian interaction (see the article titled “An introduction to the HPG Axis”), thought to be one of the leading causes of infertility. Why and how PCOS develops is not yet understood, although accumulating evidence suggests that it may be mostly genetic.2,3 Diagnosis, Symptoms and Risks A PCOS diagnosis is based on menstrual irregularity, excessive production of androgens (masculinizing hormones) or excessive masculinizing traits (such as balding, excessive body and facial hair),
Information is not intended to diagnose treat or cure any condition. Please see a qualified healthcare practitioner for information and assessment if you suspect you may be suffering from PCOS.
Polycystic ovarian syndrome is a hormone disorder affecting 5-10% of childbearing women and the most significant cause of infertility amongst women of all nationalities. Its classification as a syndrome means that there is a systemic nature and a constellation of signs and symptoms that result from disordered endocrine function. This means no two individuals with ovaries will experience it the same. Symptoms vary greatly from weight gain, acne, excessive hair growth, multiple ovarian cysts, and male pattern hair-loss. More advanced cases may also result in blood sugar dysregulation (hyperinsulinemia), elevated fats in the blood (triglycerides), and constipation and visible masses. Gone are the days when PCOS could be ruled in or out with an Ultrasound showing cysts. Instead diagnosis has become significantly more complicated. Currently in the US, the diagnostic criteria include at least two of the following: 1) light or no menses which may result in infertility or multiple miscarriages, 2) clinical or biochemical signs of hyperandrogenism (including excess coarse hair growth, male pattern baldness, and/or acne), 3) polycystic ovaries.
While there is no definitive test, we can combine the clinical picture with our understanding of an individual’s risk. The first major risk factor is genetics; there is a strong (up to 50%) risk of developing PCOS with a first-degree association with a family member who also has PCOS. A number of genes have been linked to PCOS though there is no consensus yet on which mutations will cause result in the hormonal dysregulation seen in PCOS. Obesity is another risk factor for PCOS, while, weight gain is a common symptom of PCOS. Stress can also increase the risk for atypical PCOS, since it can disturb the hypothalamic pituitary axis (HPA) which lowers most sex hormones. Further, insulin resistance means there is more insulin in the bloodstream which promotes androgen production, which then exacerbates insulin resistance. This upsets the delicate hormone balance in the body, having widespread systemic effects.
Two theories exist to explain the excess androgens (testosterone and DHEA) present in individuals with ovaries:
1. The first theory is that the rhythm of reproductive hormones from the hypothalamus and anterior pituitary are disturbed. Meaning it is a central dysfunction. Normally the little gland in our brain known as the hypothalamus releases gonadotropin releasing hormone (GnRH) which can then travel to the neighbouring pituitary gland resulting in release of luteinizing hormone (LH) and follicle stimulating hormone (FSH) (LH:FSH ratio is increased). With these levels increased follicles (or eggs) are not able to properly mature and then cannot be released (anovulation), and abnormal or no menstruation. Without ovulation of follicles, estrogen levels rise because they are unopposed. This promotes androgen production in the ovaries as well as in fat tissue where excess estrogen is converted to testosterone.
2. The second theory, that may simultaneously happen, is that women with PCOS seem to have high levels of insulin in their blood, indicating an insulin resistance. These high insulin levels contribute to this hormone dysregulation independently to the HPA axis. Insulin can stimulate the ovaries and adrenal glands to increase production of androgens and can also have an effect on the hypothalamus. Insulin also reduces the amount of sex hormone binding globulin (SHBG,) this means more androgens are floating around and available for longer than normal. This hormone dysregulation has a significant impact on fertility since women have difficulty ovulating, which can lead to the development of ovarian cysts, hence the name.
In both cases individuals may experience very significant psychological effects of PCOS, including depression, anxiety, and body dysmorphia. This can have a profound impact on well-being particularly when dealing with infertility. The overall goal of treatment is to rebalance hormones by increasing the excretion of excess estrogen, resetting the complex feedback systems that control it, promoting ovulation, and rebalancing blood sugars.
Lifestyle considerations include fat loss through high intensity interval exercise, particularly if there is significant abdominal fat present. Other steps that can help are the removal of toxic endocrine disruptors found in foods and personal care products and increasing elimination pathways, with good bacterial environments and fibre. Further, ensuring the timing of meals supports proper blood sugar management and consuming low glycemic index foods, avoiding saturated and trans-fats, and simple sugars.
Supplementation may also be indicated for certain individuals with deficiencies or genetic abnormalities. Inositol is a member of the B vitamin family comes in two forms the myo-inositol and d-chiro- inositol. It acts like a secondary messenger, communicating with cells in the brain and for resetting the “hormonal thermostats.” A combination of the two forms was shown to significantly improve insulin sensitivity by cells, thus preventing blood glucose dysregulation. This also had an impact on a regulating number of sex hormone levels. Further, oocyte and egg quality improved leading to improved fertility in women suffering from PCOS. This treatment option is particularly helpful for induvial who have significant mood disruption as it is also known to be calming while still addressing underlying cellular causes and insulin regulation.
Folate has also been seen to be beneficial by providing antioxidant support from excess homocysteine. Folate also supports healthy brain, cardiovascular and genetic functioning. It is very important to ensure that individuals are able to convert and use the folate from supplements. A genetic anomaly known as the MTHFR mutation prevents folic acid commonly found in supplements from being converted into its active form and participating in the neutralisation of a toxic product called homocysteine. So by providing the calcium-5- methyltetrahydrofolate form of folate we reduce the metabolic burden on individuals while also considering the high incidence of this mutation. Other treatments to promote healthy cellular functioning and hormone regulation include: vitamin D, and chromium picolinate, and alpha lipoic acid, supplementation to improve insulin resistance, and N-acetyl cysteine.
Artini, P.G., Di Berardino, O.M., Papini, F., Genazzani, A.D., Simi, G., Ruggiero, M., & Cela, V. Endocrine and clinical effects of myo-inositol administration in polycystic ovary syndrome: A randomized study. Gynecological Endocrinology. 2013; 29(4):375-379.
Benjamin, J., et al. Double blind placebo controlled crossover trial of inositol treatment of panic disorders. Am J Psychiatry. 1995; 52:1084-1086
Carlomagno, G., De Grazia, S., Unfer, V., & Fedele Manna. Myo-inositol in a new pharmaceutical form: a step forward to a broader clinical use. Expert Opin. Drug Deliv. 2012; 9(3):267-271.
Colazingari , S., Treglia, M., Najjar, R., & Bevilacqua, A. The combined therapy myo-inositol plus D-chiro-inositol, rather than D-chiro-inositol, is able to improve IVF outcomes: results from a randomized controlled trial. Arch Gynecol Obstet. 2013; 288:1405–1411.DOI 10.1007/s00404-013-2855-3.
Ferri, F., Polycystic Ovary Syndrome. Ferri’s Clinical Advisor. 2016. 981-982 (3). Philadelphia: Mosby.
Fux, M., et al. Inositol treatment of obsessive-compulsive disorder. Am J Psychiatry. 1996; 53: 1219-1221
Genazzani, A., et al. Differential Insulin Response to Myo-Inositol Administration in Obese Polycystic Ovary Syndrome Patients. Gynecol Endocrinol. 2012; 28(120):969-973.
Huang, G., et al. Clinical Update on Screening, Diagnosis and Management of Metabolic Disorders and Cardiovascular Risk Factors Associated with Polycystic Ovary Syndrome. Curr Opin Endocrinol Diabetes Obes. 2012; 19(6): 512-519.
Levine, J., et al. Double blind controlled trial of inositol treatment of depression. Am J Psychiatry. 1995; 152: 792-794.
Minozzi, M., Nordio, M., &Pajalich, R. The combined therapy myo-inositol plus D-Chiro-inositol, in a physiological ratio, reduces the cardiovascular risk by improving the lipid profile in PCOS patients. European Review for Medical and Pharmacological Sciences. 2013; 17: 537-540.
Nordio, M., & Proietti, E. The Combined therapy with myo-inositol and D-Chiro-inositol reduces the risk of metabolic disease in PCOS overweight patients compared to myo-inositol supplementation alone. European Review for Medical and Pharmacological Sciences. 2012; 16: 575-581.
Thomson, R., et al. The Effect of a Hypocaloric Diet with and without Exercise Training on Body Composition, Cardiometabolic Risk Profile, and Reproductive Function in Overweight and Obese Women with Polycystic Ovary Syndrome. J Clin Endocrinol Metab. 2008; 93(9):3373-3380.
Unfer, V., et al. Effects of Myo-Inositol in Women with PCOS: A Systematic Review of Randomized Controlled trials. Gynecol Endocrinol. 2012; 28(7):509-515.